“Mal de Chagas” in Europa e in Italia: un problema sommerso

Dr. Andrea AnghebenCentro per le Malattie Tropicali

Ospedale Sacro Cuore – Don CalabriaNegrar

www.tropicalmed.eu

Ten neglected tropical disease “hotspots” around the globe.

Hotez PJ (2014) Ten Global “Hotspots” for the Neglected Tropical Diseases. PLoS Negl Trop Dis 8(5): e2496.

doi:10.1371/journal.pntd.0002496

http://www.plosntd.org/article/info:doi/10.1371/journal.pntd.0002496

La malattia di Chagas è la principale malattia parassitaria per «burden» nelle Americhe

Cento e più anni di Malattia di ChagasKey facts

- About 6 million to 7 million people are estimated to be infected

worldwide, mostly in Latin America.

- Vector-borne transmission occurs in the Americas. The vector

is a triatomine bug that carries the parasite Trypanosoma cruzi which

causes the disease.

- Chagas disease was once entirely confined to the Region of the Americas – principally

Latin America – but it has now spread to other continents.

- The disease is curable if treatment is initiated soon after infection.

- In the chronic phase antiparasitic treatment can also prevent or curb/halt disease

progression.

- Up to 30% of chronically infected people develop cardiac alterations and up to 10%

develop digestive, neurological or mixed alterations which may require specific treatment.

- Vector control is the most useful method to prevent Chagas disease in Latin America.

- Blood screening is vital to prevent infection through transfusion and organ transplantation.

- Diagnosis of infection in pregnant women, their newborns and siblings is essential.

WHO fact sheet March 2015

Modalità di trasmissione

Rischio di trasmissione da:•contatto con Triatomina infetta: 0,1%•singola trasfusione di sangue (500 ml): 12-20%•trapianto renale da donatore in fase indeterminata: 35% • riattivazione in corso di immunodepressione: 30%• materno-fetale: 0,1-12%

Note epidemiologiche

Endemica in 21 Paesi dell’America Latina continentale

100 milioni di persone a rischio (25% della popolazione LA)

6-7 milioni di persone infettate (10000 decessi per anno) ↑↑↑ America Latina

Importanti variazioni endemicità tra Paesi

1.3%

1-5%

18-22%

1-5%

5-10%

1%

Aree GeografichePrevalenza

Migrazioni

La migrazione di individui affetti da malattia di Chagas pone un PROBLEMA DI SALUTE PUBBLICA NEI PAESI NON ENDEMICI…

Figure 1. Estimated number of Chagas disease cases in North America.

Hotez PJ, Dumonteil E, Betancourt Cravioto M, Bottazzi ME, Tapia-Conyer R, et al. (2013) An Unfolding Tragedy of Chagas Disease in North

America. PLoS Negl Trop Dis 7(10): e2300. doi:10.1371/journal.pntd.0002300

http://127.0.0.1:8081/plosntds/article?id=info:doi/10.1371/journal.pntd.0002300

Courtesy Ana Requena_Mendez – IsGlobal

An estimated 80.000-

120.000 cases*

90% yet unrecognized^*Jackson et al. Bull World Health Organ 2014;287:771–772

^Basile et al. Euro Surveill. 2011;16(37):19968

The estimated incidence for Europe in general is up to 35 cases per 100000

inhabitants, similar to the incidence of notified tuberculosis cases

Il tasso di sottodiagnosi è inaccettabile (99%)

Screening passivo (CMT) ed attivo (out-

reach activities) di soggetti a rischio

(soprattutto immigrati LA residenti in

Veneto-Lombardia):

1998-03/2013: 2799 persone screenate presso CMT

Risultati: Discordanti 72 = 2,57%

Positivi: 455 = 16,26%

Negativi: 2224 = 79,45

2% circa da classificare/eseguire

NB: “bias di selezione” del campione

CD control: pitfalls and obstacles

Disease features: long silent phase, aspecific symptoms,

low awareness (healthcare professionals, communities)

Migration factors: patchy distribution, internal migration,

economic problems and administrativeconstrains, fear of stigma

Unpreparedness: missing knowledge, low attention by

public health, no political committment, scarse coordination

CARATTERISTICHE CLINICHE DELLA MALATTIA

Modified from Rassi, The Lancet 2010

Storia naturale della malattia di Chagas

Neurologic

20-30% 10% <5%70% 10%

La clinica quindi

• È spesso assente (sia fase acuta >95%, che cronica 70%)

• Quando presente, è spesso aspecifica (febbricola in fase acuta, BBdx, bradicardia, stipsi nella cronica…)

• Diagnosi non facile/alla portata di tutti i laboratori

• Lunghissimo periodo tra acquisizione e manifestazione clinica/diagnosi

• Unawareness del paziente e del medico

CONTROLLO DELLA TRASMISSIONE:

(UN)PREPAREDNESS

Trasfusioni di sangue e Chagas

• La donazione di sangue spiega il 10% dei casi di Chagas.

• 20% di rischio di trasmissione

• Prevenzione? Screening universale (Francia) vs selettivo (USA, Spagna, UK…) o esclusione donatore a rischio

• Metodi inattivazione non efficaci

Selective

screening

2005

2013

1999

2009

Selective

screening

Selective

screening

(2004/33/CE and 2006/17/CE)

• A guideline from the Council of Europe entitled “Guide to preparation Use and Quality Assurance of Blood Components” (16th edition) specifically recommends performing a validated test for T. cruzi infection in donors at risk (born or have been transfused in endemic areas)

• Accordingly, the EU directive is currently out of step with the Council of Europe’s recommendations.

Policiy re-evaluation after at

least 6 months of blood donor

screening

Policiy re-evaluation after

ElCid project data collection

(2010/45/EU

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In merito al rapporto di costo/efficacia dello screening per malattia di Chagas in gravidanza è recentemente stato pubblicato uno studio spagnolo (Sicuri et al., 2011) che ne ha solidamente dimostrato i vantaggi.

Screening materno-infantile: fattibile?

Results

“Italia” 1,4%(Angheben et al., 2011)

Malattia di Chagas: focolai di trasmissione orale alimenti

2 viaggiatori italiani:

1) 2005 Santa Catarina (Brasile) da ingestione di succo di canna da zucchero (trattato e guarito, MO)

2) Turista “avventuroso” recatosi in Amazzonia (scoperto a Roma perchè donatore di sangue, Gabrielli S et al. Blood Transfus. 2013 Oct;11(4):558-62. doi: 10.2450/2013.0055-13)

Trasmissione orale

FATTORI LEGATI ALLA MIGRAZIONE/STATO DI

MIGRANTE

La migrazione italiana in America Latina

Tre ondate migratorie:

‘800: 106 emigranti partono da Genova a Santos (Brasile) fino al 1920 15-18X106 di emigrati

II ondata dopo le guerre mondiali

II ondata: professionisti e imprenditori

La migrazione latinoamericana in Italia Migrazione di ritorno (crisi economica)

Iniziata negli anni ’70

Accresciutasi soprattutto dall’anno 2000 e poi 2003 (legge Bossi-Fini del 2002corca 70000 regolarizzazioni)

Femminilizzazione elevata delle presenze (60-70%)

Un quinto dei matrimoni misti è fra donna LA e italiano

Ecuadorians: Genova 16800; Milan 13500 out

of 91000 residents in 2010

Bolivians: Bergamo 4000; Milan 1200 out of

13000 residents in 2010

Brazilians: Rome 3400; Milan 3200; Turin 2000

out of 46700 residents in 2010;

Lumbardy 13500; Veneto 6200; Lazio 5300

www.comuni-italiani.it

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Patient care: diagnosis & treatment

of congenital, acute and chronic

cases

Stop transmission: blood transfusion, organ

transplantation,vertical transmission

Chagas disease burden

Information & surveillance: Cases, transmission routes,

healtcare…

Courtesy of Pedro Albajar-Viñas, WHO’s control strategy

The “tricycle strategy”

The NECI aims

to: • Control Chagas disease in NECs• Contribute to global efforts to eliminate Chagas disease

The Non-Endemic Countries Initiative (NECI)

In 2007, WHO and PAHO convened a meeting with Chagas disease endemic and non-endemic countries.

The presence of T. cruzi infection outside Latin America has been recognized from the 28 participating countries

Courtesy of Guido Benedetti, Global Health Center – Tuscany Region - modified

David Gray/Reuters 2012 (http://www.ifrasia.com/waiting-for-a-lift/21027619.article)

Courtesy of Pedro Albajar-Viñas, WHO

John Meckley 2007 (http://www.flickr.com/photos/meckleychina/2050239366/in/pool-1498067@N21/)

Courtesy of Pedro Albajar-Viñas, WHO

FIRST SPANISH CONSENSUS DOCUMENTon Imported Chagas Disease (2005)

People WHO:

Have been born in endemic countries.

Have been born from mothers from endemic countries.

Have traveled > 1 month to rural endemic areas.

Have received a blood transfusion in endemic countries.

Screening and Diagnosis

WHO SHOULD BE SCREENED / OFFERED SCREENING ?

And WHO:

Want to donate blood and or organs / tissues.

Are pregnant women.

Have clinical symptoms compatible with Chagas Disease.

Are going to undergo immunodepression.

Screening of asymptomatic persons was not considered (2005)

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= Institutional/Local initiatives

Chagas Disease in Europe: asymptomatic people screening?

Treating women before pregnancy prevents congenital transmission

Cost-effective to screen LA mothers, newborns and relatives of positive women. If high

prevalence from mother to all relatives

Cost-

effectiveness

screening

study

ongoing –

IsGlobal,

Barcelona

Thanks